Spatiotemporal asymmetries on brain energy landscape uncover system entrapment related to depression severity

Large-scale brain activity at rest is thought to wander among a discrete set of attractor-like functional configurations shaped by underlying structural connections, yet how state-transitions are perturbed in major depressive disorder remains unknown. Here, we integrate resting-state functional imaging and diffusion-weighted structural connectivity in individuals with and without major depressive disorder to identify stable, recurring whole-brain coactivation patterns. More frequent and shorter-lived visits to a prominent salience-dominated configuration are associated with anhedonia in depression. Moreover, reduced state transitions between visual-attentional and limbic-default mode configurations are associated with greater depressive symptom severity, indicative of cognitive rigidity, and reflected as a transition preference for energetically costly trajectories despite structurally facilitated alternatives. Our findings show that the alterations in dynamic properties, transition frequencies, and energetic asymmetries define an imbalanced state-transition landscape in which the depressed brain becomes trapped between source- and sink-like attractors, providing a mechanistic interpretation of aberrant state trajectories in depression.